On the continuation of the treatment to clinical trial patients with the investigational medicinal product after trial termination

The intention of this article is to provide a brief analysis of the rights of the patients of a clinical trial to continue receiving treatment with the investigational medicinal product after termination of a clinical trial and the obligations (if any) of the pharmaceutical companies sponsoring the investigation to continue providing such product.

The purpose of the clinical trial regulation is to establish the rules that should govern clinical research with medicinal drugs for the purpose of guaranteeing their authorization under conditions of safety and reliability that are adequate to contribute to the improvement of available therapeutic treatments and to the progress of the population´s quality of life; all of this without loosing sight of the protection of the subjects participating in the investigation, whose rights and interests must be safeguarded at all times throughout the life of the investigation.

In this regard, the provisions of Royal Decree 1090/2015, of December 4, regulating clinical trials with medicinal products, the Ethics Committees for research with medicinal products and the Spanish Registry of Clinical Studies (hereinafter, the RD on clinical trials), as well as Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trial on medicinal products for human use and repealing Directive 2001/20/EC (hereinafter, the “Clinical Trials Regulation”), are considerably inspired by this will to protect clinical trial patients. Proof of this is provided by the strict requirements that these regulations establish regarding the informed consent to be given by patients prior to their participation in a clinical trial, the limitations imposed on clinical research on minors, persons with modified capacity or pregnant women, the objective liability regime established by art. 10.1. of the RD on clinical trials, the establishment of guarantees to avoid the exercise of undue influence that could condition the will of the patient, and so on.

But what can be expected by the clinical trial patients once the trial has ended?

Article 31 of RD on clinical trials superficially regulates the continuation of treatment with a drug not authorized for marketing in Spain after the end of a clinical trial, and it does so in the sense of establishing that any such treatment must be governed by the rules established in Royal Decree 1015/2009, of June 19, which regulates the availability of drugs in special situations (hereinafter, “the RD on compassionate use”), which is the rule regulating supply of unauthorized drugs under compassionate use. In addition, this article stipulates that, in the event that the sponsor were to obtain information on the administration and use of the investigational drug under compassionate use conditions, the supply of the drug would have to be done free of charge.

Therefore, patients who, within the framework of a clinical trial, have been receiving treatment with a certain investigational medicinal drug are, at the end of the trial, in the same conditions as any other patient with regard to access to said drug; such access having to comply with RD on compassionate use which, as will now be addressed, always requires the sponsor of the clinical trial or applicant for the marketing authorization having expressed its willingness to continue supplying the drug.

In this regard, Article 7 of the RD on compassionate use establishes, when regulating access to the compassionate use of investigational medicinal products, that such use may be authorized by the Spanish Agency for Medicines and Health Products (AEMPS) provided that: (i) it is referred to patients who suffer from a chronic or severely debilitating disease or whose life is considered threatened; and (ii) who cannot be satisfactorily treated with an authorized drug. In addition, the drug to be supplied under compassionate use must be subject to a marketing authorization application or be undergoing clinical trials as compassionate use in earlier stages of research is not allowed.

In addition, the aforementioned article 7 establishes that, prior to the Agency´s authorization, the sponsor of the clinical trial or applicant for marketing authorization must express its willingness to supply the investigational drug for compassionate use as well as any other relevant information in this respect. And this is the crux of the matter, since there is no legal provision in our legal system that obliges the sponsors to guarantee trial patients that the investigational medicinal product will be available for compassionate use after termination of the trial.

Although it is true that the RD on clinical trials should be conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects, and that Article 34 of the Declaration urges sponsors, investigators and host governments to provide for post-trial access to all participants who still need an intervention that has been identified as beneficial in the trial, the Declaration (which, among other things is primarily intended for physicians, not pharmaceutical companies), does not specify the respective responsibilities of each party involved in the research to ensure compliance with this principle; a specification which, on the other hand, has also not been made by Spanish legislation, as evidenced by the fact that the RD on clinical trials stays, as its predecessor, silent on the subject.

As a result, more and more Spanish healthcare centers are, through their clinical trial contract templates, trying to impose on the sponsors a contractual commitment to continue supplying the investigational drug to the trial patients after the end of the trial. This type of commitment is included, with different nuances, in the template used by the public hospitals of the region of Madrid, in the template of several Catalan centers or in that of some Galician hospitals, among others.

The problem is that, even when these inclusions are well-intentioned in the sense of wanting to look after the interests and health of the center´s patients, they do so at the cost of imposing on private companies, such as the pharmaceutical companies sponsoring clinical research, obligations beyond their own, making them responsible for assuming, at their own expense, the treatment of the patients without a specific time limit, which, if extrapolated to all hospitals and territories in which a pharmaceutical company conducts clinical research, could become an excessively demanding burden for them.

In conclusion, the search for a definitive solution to the continuation of the treatment of patients participating in a clinical trial after its termination should be approached at an institutional level by means of a weighed assessment of the different interests that converge in this field (and, most especially, those of the patients), finally materializing in the form of an imperative legal provision, which would provide this issue with greater legal certainty, not only for the benefit of the patients but also for the pharmaceutical companies themselves, which would know in advance what their responsibilities are in this respect.


Madrid, March 28th 2022.